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Biomedical subjects

G G Skellern

Publications and source records attributed to G G Skellern.

At least 37 records · Page 2Linked to original sources
PubMed1999

Intracellular localization and metabolism of the phenanthridinium trypanocide, ethidium bromide, by isolated rat hepatocytes.

1. Confocal laser scanning microscopy (CLSM) has shown that ethidium (3 ,8-diamino-5-ethyl-6-phenylphenanthridinium) bromide, an aromatic phenanthridinium trypanocide, is taken up rapidly into the nucleoli and nuclear membranes of isolated rat hepatocytes. 2. It is biotransformed by the hepatocytes and at least five metabolites have been detected by high-performance liquid chromatography (HPLC). 3. Two new metabolites, 3- and 8-N-glucuronosylethidium, have been identified by HPLC-electrospray mass spectrometry and they represent the major pathway of metabolism, accounting for 6.4 +/- 0.7 and 19.5 +/- 1.2% respectively of total recovered drug after incubation. A third metabolite, 3,8-diacetylethidium, is formed in trace quantities. 4. The other two metabolites, 3-acetylethidium and 8-acetylethidium, have been reported previously.

Animals↗
PubMed1998

Use of capillary electrophoresis in the study of ligand-DNA interactions.

Free solution capillary electrophoresis (FSCE) has been used to separate two non-self-complementary 12mer oligonucleotide duplexes: d(AAATTATATTAT).d(ATAA-TATAATTT) and d(GGGCCGCGCCGC).d(GCGGCGCGGCCC). Titration of mixtures of the two oligonucleotides with model intercalators (ethidium bromide andactinomycin D) and minor groove binders (netropsin, Hoechst 33258 and distamycin) has shown the suitability of FSCE as a method to study the sequence selectivity of DNA binding agents. Binding data have shown cooperativity of binding for netropsin and Hoechst 33258 and have provided ligand:DNA binding ratios for all five compounds. Cooperativity of netropsin binding to a 12mer with two potential sites has been demonstrated for the first time. Ligands binding in the minor groove caused changes in migration time and peak shape which were significantly different from those caused by intercalators.

Binding, Competitive↗
PubMed1998

Separation of pd(GC)12 from pd(AT)12 by free solution capillary electrophoresis.

The two synthetic self complementary oligonucleotides pd(AT)12 and pd(GC)12 were separated by free solution capillary electrophoresis (CZE) using simple borate buffers. The effects of pH (7.5-9) and the concentration of the buffer (0.03-0.35 M) were investigated. Higher pH values and buffer concentrations led to better resolution and longer migration times, the pH having a more pronounced effect on the separation than the concentration of the buffer. It is proposed that the conformation and effective length of the oligonucleotides may have a role in their separation in free solution capillary electrophoresis.

Boric Acids↗
PubMed1998

HPTLC and HPLC determination of isometamidium in the presence of its manufacturing and degradation impurities.

The determination of the phenanthridine trypanocide, isometamidium chloride hydrochloride (ISM), in the presence of four process-related and degradation impurities, by RP-HPLC using a Licrospher-60 RP-select B column with a mobile phase composition of acetonitrile/KH2PO4 (PH 3.0, 20 mM) (25:75 v/v) with UV detection at 320 nm, is described. The method is selective, reproducible and precise with a limit of detection of 45 ng ml-1 for ISM. A HPTLC system (Kieselgel 60 F254, pyridine/acetonitrile/butanol/formic acid, 6:6:4:1, v/v), with UV densitometric evaluation at 320 nm, suitable for the separation of ISM and the related substances is reported.

Chromatography, High Pressure Liquid↗
PubMed1996

Development of a liquid chromatographic method for the control of related substances in chlorprothixene hydrochloride.

The development of a reversed-phase liquid chromatographic method, using a mobile phase containing a mixture of anion and cation ion-pairing agents and a base-deactivated octyldecylsilyl column as stationary phase, is described for the control of all known impurities in (Z)-chlorprothixene hydrochloride (bulk drug). Validation of the method showed it to be reproducible, selective for both (Z) chlorprothixene hydrochloride and its E-isomer, accurate and linear over the concentration range of analysis with a limit of detection of 0.3 microgram ml-1.

Antipsychotic Agents↗
PubMed1996

Comparative study of the determination of bupivacaine in human plasma by gas chromatography-mass spectrometry and high-performance liquid chromatography.

A comparison was made between high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) as methods for determining bupivacaine in human plasma. Both methods utilized pentycaine as an internal standard, were found to be linear in the range 5-320 ng and had acceptable precision and accuracy. The precision for the HPLC method was better than that for the GC-MS method. The limits of detection of the HPLC and GC-MS methods were ca. 1.0 and 0.1 ng, respectively. Good agreement between the HPLC and GC-MS methods was obtained for the analysis of samples taken from a patient receiving bupivacaine topically. For most purposes the HPLC method would be slightly better. However, for samples containing interfering peaks GC-MS provides a higher degree of resolution from such interferants.

Administration, Topical↗
PubMed1994

Carrier-free 131I-meta-iodobenzylguanidine: comparison of production from meta-diazobenzylguanidine and from meta-trimethylsilylbenzylguanidine.

Meta-iodobenzylguanidine (MIBG) is a drug which is selectively accumulated by the uptake-1 process in adrenergic tissues. When labelled with 131I, it may be used for the targetted radiotherapy of tumours such as phaeochromocytoma and neuroblastoma. This paper describes the preparation of carrier-free 131I-MIBG by radioiodination of meta-diazobenzylguanidine, and compares this process with one involving iododesilylation of meta-trimethylsilylbenzylguanidine. Both processes result in the formation of carrier-free 131I-MIBG whose specific activity at greater than 3 x 10(16) Bq mol-1 is at least 100 times higher than that of commercially available 131I-MIBG for therapeutic use. The therapeutic use of 131I-MIBG with a higher than usual specific activity is predicted to result in a greater target-to-nontarget ratio, and therefore enhanced efficacy because of an increased therapeutic index. As the radiochemical yield of the process involving the metadiazobenzylguanidine intermediate is only 13%, compared with 98% for the iododesilylation reaction, the latter is the preferred synthetic route.

3-Iodobenzylguanidine↗
PubMed1993

Bumetanide binding to normal albumins and to albumin in renal failure.

Binding of bumetanide, a loop diuretic, to partially purified albumins from renal failure patients (RF-HA), and healthy subjects (N-HA), human serum albumin (HSA) and defatted-HSA (D-HSA), was studied with equilibrium dialysis at a constant albumin concentration and various ligand concentrations. Binding parameters (n and K) were estimated from Scatchard plots and with a non-linear two-binding site model computer program, assuming two classes of independent sites. The binding capacities (n1K1) decreased in the order N-HA > RF-HA > D-HSA > HSA. Computer estimates of K1 for the partially purified albumin preparations were not markedly different. However, the graphical estimate of K1 for N-HA was greater than that for RF-HA. When the degree of binding (r) was plotted as a function of the logarithm of the free bumetanide concentration, an asymptotic plateau was not observed, indicating that the protein binding sites were not saturated. Consequently, the calculated binding estimates may not adequately describe the binding of bumetanide.

Albumins↗
PubMed1991

The analysis of thiocarbamides by gas chromatography/negative-ion chemical-ionization mass spectrometry.

Thiocarbamides were converted to their di-N-pentafluorobenzyl (PFB) derivatives and analysed by gas chromatography/negative-ion chemical-ionization mass spectrometry with methane as reagent gas. The PFB derivatives of the 2-thiouracils gave mass spectra in which the ion current was carried largely by an ion arising from [M-PFB]-. The derivative was used in the determination of the uptake and metabolism of thiocarbamides by cultures of melanoma cells.

Gas Chromatography-Mass Spectrometry↗
PubMed1990

Metabolism of the diuretic bumetanide in healthy subjects and patients with renal impairment.

The pharmacokinetics and metabolism of orally administered bumetanide were studied in five healthy subjects and in five patients with renal insufficiency. Healthy subjects excreted 51% of the dose as unchanged drug in the urine, whilst the patients with renal insufficiency excreted only 11% of the dose as bumetanide. Similarly the urinary excretion of the gamma-hydroxybutyl metabolite was reduced from 6% in healthy subjects to 2.3% in patients with renal impairment. In both groups of subjects the mean elimination half-life of the metabolite was greater than for bumetanide. The results indicate a possible accumulation of bumetanide and metabolite in patient with renal failure.

Aged↗
PubMed1988

Co-oxidation of arachidonic acid and methimazole by prostaglandin endoperoxide synthetase.

The thiocarbamide methimazole stimulated O2 utilisation when added to reaction mixtures containing ram seminal vesicle microsomes (prostaglandin endoperoxide synthetase preparation) and arachidonic acid. This stimulation increased with increasing methimazole concentrations, as did the production of prostaglandin E. 2-[14C]Methimazole was co-oxidized to 1-methyl-2-[14C]imidazole.

Animals↗
PubMed1984

Binding of [3H]mianserin to bovine serum albumin, human serum albumin and alpha 1-acid glycoprotein.

Scatchard plots which were curvilinear with negative slopes were obtained when the binding of [3H]mianserin to bovine serum albumin (BSA), human serum albumin (HSA), defatted human serum albumin (D-HSA) and alpha 1-acid glycoprotein (alpha 1-AGP) was studied with equilibrium dialysis with constant protein concentrations and various ligand concentrations. Binding parameters were estimated graphically and with a non-linear least-squares computer program, assuming two classes of independent binding sites. alpha 1-AGP had the highest binding affinity (K) and binding capacity (nK). The binding parameters, n and K were not independent of protein concentration when the BSA concentration was varied. Linear atypical Scatchard plots with positive slopes were obtained when the protein concentration was varied for BSA, HSA and D-HSA, at a fixed ligand concentration.

Animals↗
PubMed1983

The role of porcine thyroid peroxidase and FAD-containing monooxygenase in the metabolism of 1-methyl-2-thioimidazole (methimazole).

The peroxidase and FAD-containing monooxygenase activities of porcine thyroid subcellular preparations were measured and it was observed that FAD-containing monooxygenase activity was considerably lower than that of peroxidase. The end product of 1-methyl-2[14C]thioimidazole oxidation catalysed by thyroid peroxidase was confirmed to be 1-methylimidazole by mass spectrometry. In the presence of thyroid peroxidase 1-methyl-2-thioimidazole would appear initially to be oxidised to bis(1-methylimidazole)-2,2'-disulphide. The extent of oxidation was dependent on the iodide concentration in the reaction mixture.

Animals↗
PubMed1983

NMR studies and GC analysis of the antibacterial agent taurolidine.

The NMR spectrum of taurolidine in deuterium oxide was compared with spectra obtained from model experiments with amines and formaldehyde. Head-space analysis combined with capillary GC showed that there was less than 0.004% free formaldehyde present in 2% solutions of taurolidine. This value is comparable to the concentration of formaldehyde found when the taurolidine solutions were injected directly onto GC columns.

Anti-Infective Agents↗